Determining the structure of proteins by X-ray crystallography is an elegant and reliable method and is the basis of structure-based ligand design in which small molecules are synthesized as potential ligands for the protein of interest. This is an intense area of research for the optimisation of ligands to drugs for therapeutically interesting proteins (see Babine, R. E. and Bender, S. L., Chemical Reviews, 97, 1359–1472 (1997) and Bohacek, R. S., et al., Med. Res. Rev., 16, 3–50 (1996)).
One method of ligand screening is described in WO 99/45379, in which a library of shape-diverse compounds thought to be potential ligands are soaked or co-crystallised with a target protein, and then the resulting complex is analysed by X-ray crystallography to determine the nature of the ligand which has bound. The library of compounds which is used in the screening process generally comprises previously characterised compounds.